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- W3080905272 abstract "e19026 Background: COX-2 is often overexpressed in NSCLC leading to high systemic PGE 2 levels that in turn play a role in NSCLC pathogenesis. Changes in urine PGE-M (the major PGE 2 metabolite) reflect changes in systemic & intratumoral PGE 2 [Csiki et al. Clin Cancer Res 11:6634, 2005]. A ≥70% decline in PGE-M in NSCLC patients (pts) treated with celecoxib (C) (400 mg bid) + docetaxel (D) was associated with an apparent survival benefit [Ibid]. To effect maximum COX-2 inhibition we tested a higher C dose in a subsequent phase II trial. Methods: Eligibility: previously treated NSCLC, PS 0–2, evaluable/measurable disease, adequate marrow, renal & hepatic function, no current NSAID or sulfa allergy. Urine PGE-M measured prior to & 5–10 days after C 600 mg PO bid. Pts with ≥70% decline in PGE-M continued on C + D 75 mg/m 2 or pemetrexed 500 mg/m 2 q3wk x 4 cycles followed by maintenance C 400 mg PO bid until PD or drug intolerance. Results: 21 pts enrolled; F=7, M=14; 2 ineligible (1 carcinoid; 1 elevated LFT); 2 stopped C early (1 ARF; 1 pruritus). Mean PGE-M levels decreased from 38.9 to 7.8 ng/mg Cr pre- & post-C (mean change = 80%; P=0.002). The mean decline was greater in current & former smokers (81%; P=0.002) compared to never smokers (46%; P=0.19). Males had higher pre- treatment PGE-M (44 vs. 28.8 ng/mg Cr; P=0.21). Males had a significant decrease in mean PGE-M levels after C (78%; P=0.011); a similar albeit not significant change occurred in females (P=0.12). 12 screened pts (57%) had a ≥70% decline in PGE-M & received treatment with C + chemotherapy; 8 pts are evaluable for response; SD = 6; PD = 2. Treatment was well tolerated with no cardiac toxicities noted. Conclusions: These preliminary data indicate C 600 mg bid effectively inhibits intratumoral COX-2 in >50% NSCLC pts, a higher percentage than our previous trial using C 400 mg bid. The effect is greatest in former & current smokers & males compared to never smokers & females. Toxicities are acceptable. Accrual is ongoing. [Funding: VICC Lung Cancer SPORE CA90949]. No significant financial relationships to disclose." @default.
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- W3080905272 date "2009-05-20" @default.
- W3080905272 modified "2023-09-24" @default.
- W3080905272 title "Urine PGE-M to assess prostaglandin E2 (PGE2) levels in non-small cell lung cancer (NSCLC)" @default.
- W3080905272 doi "https://doi.org/10.1200/jco.2009.27.15_suppl.e19026" @default.
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